Macrophage precursor cells from the left atrial appendage of the heart spontaneously reprogram into a C-kit +/CD45 − stem cell-like phenotype. (15th April 2016)

• Record Type: Journal Article
• Authors: Leinonen, Jussi V.; Korkus-Emanuelov, Avishag; Wolf, Yochai; Milgrom-Hoffman, Michal; Lichtstein, David; Hoss, Sara; Lotan, Chaim; Tzahor, Eldad; Jung, Steffen; Beeri, Ronen
• Is Part Of: International journal of cardiology. Volume 209(2016)
• Page Start: 296
• Page End: 306
• Publication Date: 2016-04-15
• Subjects: Adult stem cells -- Macrophages -- Cell transdifferentiation -- Atrial appendage -- Heart; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2016.02.040
• Languages: English
• ISSNs: 0167-5273

Abstract

Abstract: Background: The developmental origin of the c-kit expressing progenitor cell pool in the adult heart has remained elusive. Recently, it has been discovered that the injured heart is enriched with c-kit + cells, which also express the hematopoietic marker CD45. Methods and results: In this study, we characterize the phenotype and transcriptome of the c-kit +/CD45 +/CD11b +/Flk-1 +/Sca-1 ± (B-type) cell population, originating from the left atrial appendage. These cells are defined as cardiac macrophage progenitors. We also demonstrate that the CD45 + progenitor cell population activates heart development, neural crest and pluripotency-associated pathways in vitro, in conjunction with CD45 down-regulation, and acquire a c-kit +/CD45 −/CD11b −/Flk-1 −/Sca-1 + (A-type) phenotype through cell fusion and asymmetric division. This putative spontaneous reprogramming evolves into a highly proliferative, partially myogenic phenotype (C-type). Conclusions: Our data suggests that A-type cells and cardiac macrophage precursor cells (B-type) have a common lineage origin, possibly resolving some current conundrums in the field of cardiac regeneration.